1. Field of the Invention
The present invention relates generally to the fields of molecular biology and pharmacology. More particularly, it concerns the use of abscissic acid to treat various diseases, including neurodegenerative diseases and neuromuscular diseases.
2. Description of Related Art
Although increases in iron have been associated with several diseases, synthetic chemical chelators of iron have side effects that prevent their widespread use in human medicine. Additionally, most synthetic chelators do not penetrate the blood-brain barrier and are thus of very little clinical use (e.g., in treating neurodegenerative diseases such as Parkinson's Disease).
Ferritin H (FH) is a protein which can chelate iron, and FH is produced by organisms including mammals. It has been shown that ferritin-H can also repress the human beta-globin gene (U.S. Application 2002/0128183, incorporated herein by reference in its entirety without disclaimer). Thus, ferritin H could be beneficial in treating diseases which are caused and/or characterized by increases in iron (e.g., Alzheimer's Disease, Parkinson's Disease) and/or diseases which are characterized by the production of a dysfunctional beta-globin (e.g., sickle cell anemia).
There exists a need to selectively induce FH expression with a compound that may be used clinically. Several compounds may be used to induce FH expression; however, problems including lack of selectivity and/or undesirable systemic effects can result from these compounds. For example, free iron itself can induce ferritin synthesis in cells through a regulation that occurs at the translational level of gene expression. However, this induction is not selective since both FH and ferritin-L (ferritin light chain, FL) are produced. Furthermore, the amount of ferritin induced by this mechanism is unlikely to correct the problem of iron overload. Gene therapy administration of ferritin H is described in U.S. application 2002/0128183, which is incorporated by reference herein in its entirety without disclaimer.
Cytokines such as IL-1β, TGFβ, and TNFα may cause a more specific induction of FH at the transcriptional level of gene expression (i.e., selective in the sense that the ferritin-L gene does not respond to these stimuli). However, these cytokines cause significant unwanted systemic effects in humans and experimental animals such as inflammation, thus limiting their clinical potential.
Retinoic acid, a form of vitamin A, is also a ferritin-H inducer. However, high doses of retinoic acid can result in vitamin toxicity.